[3H]Paroxetine binding to the serotonin transporter has been shown to be altered in brain tissue from schizophrenic subjects. Some schizophrenic subjects are treated with antidepressant drugs, some of which bind to the serotonin transporter and their time of death is variable. To determine if these confounding factors could affect [3H]paroxetine binding, [3H]paroxetine binding to cortical membrane from rats treated with the antidepressant drugs for 10 or 28 days and in non-treated rats that were killed at different times of the day was measured. Drug treatment, when compared to injection with 0.9% saline and time of death, did not affect [3H]paroxetine binding. Treatment with imipramine [10 days: mean +/- S.D.: 590 +/- 59 fmol/mg protein (P < 0.05); 28 days: 653 +/- 59 fmol/mg protein (P < 0.01)] or mianserin [10 days: 600 +/- 43 (P < 0.05)] caused a significant decrease in the density of [3H]paroxetine binding compared to that in fluoxetine-treated rats (10 days: 820 +/- 211 fmol/mg protein; 28 days: 764 +/- 100 fmol/mg protein). Thus, overall, these data do not suggest changes in [3H]paroxetine binding reported in the human brain tissue would be due to antidepressant drug treatment or time of death.