Kinetic constants of platelet imipramine binding were determined in youths with major depression and a contrast group. Subjects actively depressed (N = 10) had significantly fewer imipramine binding sites (B(max)) (877 +/- 148 fmol/mg protein) than recovering depressives (N = 12) (1220 +/- 428 fmol/mg protein) and contrasts (N = 10) (1270 +/- 230 fmol/mg protein). Affinity constants (K(d)) (1.14 +/- 0.36 nM, 0.97 +/- 0.31 nM, and 1.17 +/-0.39 nM, respectively) were similar among the groups. Actively depressed males but not females had fewer imipramine binding sites than both their sex-matched comparison groups, Although actively depressed females' B(max) was significantly lower than recovering depressed and nondepressed males, neither age, Tanner stage, nor circannual rhythms influenced B(max), but suicidality may be associated with low B(max) A decrease in B(max) may be a state-specific marker of major depression in boys or associated with a depressive disorder with a suicidal history.