Baclofen, a GABAB agonist, decreases both the maintenance and reinstatement of i.v. cocaine-reinforced responding in rats. In the present experiment the effects of baclofen were extended to a comparison of male and female rats during the acquisition of i.v. cocaine self-administration. Four groups of rats were trained to self-administer i.v. cocaine (0.2 mg/kg) under a fixed-ratio 1 (FR 1) schedule using an autoshaping procedure. The criterion for acquisition was a 5-day period during which a mean of 100 cocaine infusions were administered. Rats were given 30 days to reach this criterion. Male and female groups (n = 10-13) were pretreated with i.p. injections of baclofen (2.5 mg/kg) or vehicle 30-min prior to the sessions. A subset of rats (N = 5) that did not acquire cocaine self-administration continued to be exposed to the acquisition procedure after baclofen treatment ended. Pretreatment with baclofen decreased both the rate of acquisition of cocaine self-administration and the percentage of rats meeting the acquisition criterion to a greater extent in females than in males. Female rats that did not meet the acquisition criterion with baclofen treatment, acquired within a few days after treatment ended. The findings confirm previous reports of enhanced acquisition of cocaine self-administration in females versus males, and they indicate that baclofen suppressed the acquisition of cocaine self-administration significantly more in females than in males.