Immunocytochemical evidence suggests that the neuroendocrine Dahlgren cells of the teleost caudal neurosecretory system (CNSS) are innervated by descending serotonergic fibres, However, the modulatory effect(s) of 5-hydroxytryptamine (5-HT) on the activity of the CNSS are not known, The present study investigates the effect of superfusion of 5-HT and the selective 5-HT, receptor agonist 5-carboxamidotryptamine (5-CT) on the electrophysiological properties of Dahlgren cells recorded intracellularly in an isolated CNSS preparation from the flounder, Superfusion of 5-HT (10(-7)-10(-3)M) caused a concentration-dependent, reversible hyperpolarization of the resting membrane potential (E-m) of cells previously identified as 'Type 1' (putative urotensin I-secreting) cells (control = -63.5+/-1.5 mV; 10(-4)M 5-HT = -95.0+/-0.9 mV, n=6, P<0.01). The EC50 was 7.6+/-4.1 mu M (n=6). Hyperpolarization resulted in a reduction or cessation of firing of these cells, suggesting an inhibitory role for the serotonergic input to the CNSS. Hyperpolarization was accompanied by a concomitant decrease in the membrane input resistance (control =16.6+/-2.8 M Omega; 10(-4)M 5-HT=6.4+/-1.3 M Omega; n=6, P<0.05) and time constant (control = 60.3+/-13.1 ms; 10(-4)M 5-HT = 16.0+/-4.4 ms, n=6, P<0.05). These effects were mimicked by the superfusion of much lower concentrations of 5-CT (EC50=47.1+/-7.1 nM, n=4) suggesting that they are possibly mediated by a 5-HT1 receptor subtype, if the teleost 5-HT1 receptor has a markedly higher affinity for 5-CT than 5-HT1 in common with mammalian 5-HT1 receptors. In contrast to the findings in Type 1 cells, cells identified as 'Type 2' (putative urotensin It-secreting) did not respond to either 5-HT or 5-CT, suggesting that the serotonergic input into the CNSS plays no role in the modulation of activity of this sub-population of neuroendocrine cells, Accordingly, these data suggest a functional difference between Type 1 and Type 2 Dahlgren cells, previously differentiated only on electrophysiological criteria and spatial distribution within the CNSS.