In the present investigation, the neuropharmacology of 1,3 butanediol (1,3-BD) was compared with that of ethanol. Acute i.p. administration of equimolar doses of 1,3-BD or ethanol to rats impaired the aerial righting reflex, attenuated the suppressive effect of punishment on drinking behavior, lowered blood pressure, caused a concomitant reduction in the content of guanosine 3',5'-monophosphate in the cerebellum and reduced ethanol withdrawal reactions. Although these data suggested that ethanol and 2,3-BD were of similar potency, the brain content of 1,3-BD was only 33% of that of ethanol after treatment with equimolar doses, suggesting a greater central nervous system (CNS) potency for 1,3-BD. In rats treated chronically with ethanol to produce physical dependence, 1,3-BD was more potent than ethanol in inhibiting the hyperexcitability observed upon ethanol withdrawal. Furthermore, chronic administration and withdrawal of 1,3-BD caused CNS hyperexcitability in rats that was characteristic of physical dependence. Despite these similarities, there were clear differences in the actions of ethanol and 1,3-BD. In mice, locomotor stimulation caused by ethanol was not observed after 1,3-BD. Furthermore, while 1,3-BD did not alter the concentration of luteinizing hormone in plasma, equivalent doses of ethanol markedly reduced the concentration of this hormone. These data indicate that like ethanol, 1,3-BD depresses CNS activity and induces physical dependence, but has less effect on plasma luteinizing hormone concentration than ethanol.