Discrepant results have been reported from at least ten laboratories regarding the status of platelet alpha 2 adrenoreceptors in depressed patients. Using a statistical test to combine those studies which utilized radioligand binding techniques, we find the overall data support an elevation in density of platelet alpha 2 adrenoreceptors from drug-free depressed patients (p less than 0.05) and suggest a normalization to lower binding values following antidepressant drug treatment (0.05 less than p less than 0.10). However, these positive results are attributable to highly significant findings by only three laboratories. Much of the discrepancy may be attributable to numerous methodological variables which distinguish the studies. Foremost amongst these variables are the use of different platelet size populations, the use of different medium, and the choice of radioactive ligand and competitor (non-radioactive ligand) in the assay. We present a rationale for the proper choice of each methodological condition used in the clinical assessment of platelet alpha 2 adrenoreceptor status, hoping that improved experimental designs will resolve the current controversy.