Tritiated imipramine binding to whole platelets was measured in 16 chronic pain patients who were free from major depression, and in a control group. The maximum binding was significantly lower in chronic pain patients than in the control group, whereas the binding affinity was not significantly different. Twelve patients were treated with mianserin for 21 days; this produced a significant improvement in the mean scores for pain (evaluated with the McGill Questionnaire) and depressive symptoms (assessed with the Zung Self-Rating Scale). The improvement in both types of symptom was accompanied by a significant mean increase in the density of the [3H]imipramine binding sites without modifications in the values of the constant of affinity. All the patients who responded well to treatment (N = 8) had a family history of depressive spectrum disorders (DSD), while none of those who failed to respond had a first degree relative with DSD.