This study determined the dose-response effects of inhaled salbutamol (SAL) on time-trial performance and urine concentrations of SAL (cSAL). Methods: Nonasthmatic, trained male cyclists and triathletes (N = 37) were studied. Day I consisted of screening for airway hyperresponsiveness, using a eucapnic voluntary hyperpnea test (EVH), followed by an incremental exercise test to determine VO2max and peak power (P-max). On days 2-5, athletes performed a 20-km time trial 15 min after inhalation (PI) of placebo, 200 mu g (132), 400 mu g (D4), or 800 mu g (138) of SAL. At 60 min PI, urine samples were provided. All conditions were randomized and double blinded, with repeated-measures ANOVA used to determine effects of dose. Post hoc analysis was done with Tukey's HSD test. Results: Seven subjects had positive responses to the EVH test, resulting in a 19% incidence within this sample; they were excluded from further participation in this study. The remaining subjects (N = 30) had a VO2max of 67.1 (4.3) mL.kg(-1).min(-1) and P-max of 457 (31) W (W). There was no effect of dose on completion time (P > 0.05), mean power (P > 0.05), or mean heart rate (P > 0.05). Similarly, SAL had no effect on any metabolic or ventilatory parameters (P > 0.05). Urine cSAL increased with dose and was highly variable, with the peak value observed being 831 ng.mL(-1) after a dose of 800 mu g. Moderate but significant correlations were noted between cSAL and urine specific gravity at higher doses (D4, r = 0.42; D8, r = 0.37). Conclusions: These findings suggest that inhaled SAL does not enhance time-trial performance, regardless of dose, and that urine cSAL after exercise is related to dose, demonstrates high variability, and is partially related to hydration status.