Recent findings of reduced 3H-imipramine binding in platelets of depressed patients compared to healthy controls have been proposed as a biological marker of depression. However, these studies failed to consider the possible occurrence of seasonal variation in the binding characteristics. Our results show a highly significant seasonal variation in platelet 3H-imipramine binding which occurs in both normal and depressed populations. Furthermore, when annual rhythms are taken into account, there is no difference in the binding parameters in the two populations.