Ninety-four Belgian White and Blue double-muscled calves were involved in this study which aimed to compare the efficacy of a serotonin-S2 receptor blockade at two different stages of an acute respiratory distress syndrome (ARDS), i. e. at the occurrence of first clinical signs or when another anti-inflammatory compound was clinically shown to be ineffective. Metrenperone, a 5-hydroxytryptamine (5-HT2) blocker, was injected (intramuscularly, 5 times, at 12 hourly intervals, dose rate: 0.1 mg/kg) to (1) 58 calves referred to our laboratory after a treatment (group I) which lasted from 3 to 5 days and which did not improve the clinical status of the animals and (2) 36 calves investigated as soon as first clinical signs occurred (group II). Following the severity of the ARDS, the animals from group I needed to be classified into 2 groups: group I(A) (moderate ARDS - n = 45) and group I(B) (severe ARDS - n = 13). For animals in group I, the antibacterial compound previously used was maintained and administered during 4 more days whilst the previous anti-inflammatory drug was suppressed and replaced by metrenperone administered as mentioned above. In group II, each animal was treated with ceftiofur sodium as an antibacterial agent. A clinical score and a breathing score were calculated at each step of the investigation period, i. e. before (T0) and 1 hour (T1) after the first treatment, during the interval 12 H - 48 H (T2) which followed this treatment and 168 H (T3) after this treatment. Four clinical parameters were also taken into account separately: rectal and cutaneous temperatures, respiratory and heart rates. Over the whole investigation period, respiratory rate registered in the three groups decreased linearly but differently (slopes: -0.02842, -0.09312 and -0.0893 in groups I(A), II and I(B) respectively) while clinical scores of grouPS I(A) and II were linearly and similarly (slope: -0.002673) improved. Furthermore, during the period evolving from 1 hour to 24 hours after the first injection of metrenperone, cutaneous temperature increased linearly in group I(A) (slope: 0.031) and II (slope: 0.108). Compared to values recorded at T0, the breathing scores registered at T2 were significantly improved in groups I(A) and II while those obtained at T3 were improved only in group II. In group I(A), all animals survived and the 95 % Confidence Interval (C.I.) for the survival probability was [0.92, 1.00] whilst the observed survival proportion value and C.I. relative to group II were 0.94 and [0.81, 0.99] respectively. It was concluded that, in double-muscled calves affected by a naturally occurring ARDS, a treatment combining metrenperone and an antibacterial compound, (1) induced a clinical improvement, which appeared at a later stage in animals severely affected by the ARDS, (2) enabled a clinical improvement in animals which did not show any signs of clinical improvement when treated by usual therapeutic drugs.