Objective: Abnormalities in the serotonergic system have been implicated in suicidal behavior. Higher numbers of serotonin-2 (5-HT2) receptors have been reported in the post-mortem brain of suicide victims. In order to further examine the role of 5-HT(2A) receptors in suicidal behavior, the authors studied 5-HT(2A) receptors in platelets of suicidal and nonsuicidal patients as well as normal comparison subjects. Method; 5-HT(2A) receptor levels were determined by using [125I]LSD as a radioligand in platelets obtained from hospitalized psychiatric patients (N = 131) and nonhospitalized normal comparison subjects (N=40) during a drug-free baseline period. Patients were diagnosed according to DSM-III-R criteria, and suicidal behavior was identified by using the Hamilton Depression Rating Scale. Results: The mean maximum number of binding sites (B(max)) of platelet 5- HT(2A) receptors for all suicidal patients was significantly higher than for nonsuicidal patients or normal comparison subjects. This significant difference remained when subgroups of suicidal patients with depression, schizophrenia, schizoaffective disorder, or bipolar illness were compared to the other two subject groups. The higher number of platelet 5-HT(2A) receptors in suicidal patients was independent of diagnosis. While there was no significant difference in B(max) between patients with serious suicidal ideation and those who made suicidal attempts, both groups had significantly higher B(max) than normal comparison subjects. Conclusions: The observed higher number of platelet 5-HT(2A) receptors in suicidal patients is independent of diagnosis and appears to be associated with both the brain and the platelets of suicidal patients. These results thus suggest the potential usefulness of platelet 5-HT(2A) receptors as a biological marker for identifying suicide-prone patients.