BACKGROUND Our investigation involved a quantitative literature review technique known as meta-analysis to compare the efficacy of three newer antidepressants and imipramine. METHODS We examined seven major journals in psychiatry from 1980 through 1990, inclusive, and selected those investigations of imipramine, trazodone, bupropion, and fluoxetine that met our minimal criteria for interpretability. These criteria included: (1) the presence of a placebo control, (2) double-blind status, (3) the use of the Hamilton Rating Scale for Depression as a dependent variable measure, (4) the use of nongeriatric adults with a diagnosis of major depression by DSM or RDC standards, and (5) the presence of reported means and standard deviations in the investigation, or sufficient data that allowed such to be computed. Each study of four antidepressants was analyzed for an effect size of the drug investigated. The effect size allows for a determination of the efficacy of a particular drug as compared with placebo, measured in standard deviation units. RESULTS The data indicated that all four agents are effective as compared with placebo. Furthermore, there is no evidence that the newer heterocyclic agents are less effective than imipramine, as an ANOVA showed no statistically significant difference between the effect sizes of the four antidepressants. CONCLUSIONS These data are discussed in terms of characteristics of the various investigations and the need for further research comparing the efficacy of psychopharmacologic agents.