The specific binding to platelet membranes (B~,) of 3H-clonidine, an alpha-2 agonist, and 3H-yohimbine, an alpha-2 antagonist, was measured in nine drug-free male schizophrenic patients and repeated after 2 weeks of chlorpromazine (CPZ) treatment. Patients with a lower pretreatment B,~,~ for 3H-clonidine showed a significantly smaller change in B~,~ after treatment, less improvement in their clinical state, as indicated by the change in the Global Assessment Scale (GAS), and a lower posttreatment GAS. Also, they had a significantly higher score for negative symptoms on the Affect Rating Scale both before and after treatment. These findings suggest that schizophrenic patients with relatively subsensitive platelet alpha-2-adrenergic receptors, as measured by 3H-clonidine binding, tend to have more negative symptoms and a diminished alpha receptor binding response and diminished clinical response to CPZ. There were no clinical correlations to 3Hyohimbine binding.