We studied the effect of in vitro and in vivo treatment with the tricyclic antidepressant clomipramine on spontaneous mobility and on N-formyl-l-methionil-l-leucyl-l-phenylalanine (fMLP)-induced chemotaxis of rat peritoneal macrophages. When added in vitro clomipramine was able to diminish (from 10⁻⁴ to 10⁻⁷ M) both spontaneous and stimulated migration of macrophages. A similar effect was observed after the in vivo administration of the drug. In fact, both spontaneous and fMLP-induced mobility of peritoneal macrophages in vitro were significantly reduced after the subcutaneous injection of 20 and 40 mg/kg of clomipramine in comparison to the chemotaxis of macrophages obtained from saline-treated animals. These results give further evidence that psychoactive drugs can affect some immune parameters, and could contribute to explain the antiinflammatory action of clomipramine.