Since the discovery that clomipramine was effective in the treatment of obsessive-compulsive disorder (OCD), trials of several different medications for OCD have been published. The question of which agent, if any, is the medication of choice in OCD is of real clinical concern. Published clinical trials were collected using computerized search on MedLine and PsychLit. Trials that met predetermined criteria were included in a meta-analysis. Analyses of variance were used to compare the specific effect sizes of different medications in OCD. In placebo-controlled trials, serotonin reuptake inhibitor (SRI) type had a significant effect on medication effect size, with clomipramine more effective than fluoxetine. Although this finding did not alter when trials were restricted to those with large numbers of subjects (n > 50), the analysis was based on a very limited number of studies. The fact that so few placebo-controlled studies have been done in OCD compromises the findings of this meta-analysis. It would be premature to extrapolate the results to clinical practice, where clomipramine and certain selective SRIs are currently and justifiably used as first-line agents. Nevertheless, the current study supports previous work suggesting that increased serotonergic specificity is not necessarily correlated with greater efficacy in the treatment of OCD. Further head-to-head comparison studies are necessary to confirm or refute this preliminary impression.