Fatty acid composition was quantitatively analyzed in RBC ghost membranes of 20 schizophrenic patients stabilized with haloperidol (5-20 mg/day) and of the same individuals after haloperdol (HD) withdrawal. The average days on medication and drug-free period were 52 and 40 days, respectively. No significant differences were demonstrated in levels (% or nmol/ml packed RBC) of polyunsaturated fatty acids (PUFAs) between HD-treated and drug-free patients. Similarly, no significant difference was found between relapsed and nonrelapsed schizophrenic patients, although the mean levels of 20:4 (n - 6), total PUFAs or fatty acid unsaturation index (FAUI) were consistently higher in nonrelapsers than in relapsers. On the other hand, the decreases in FAUI were significantly (r = -0.46, p = 0.04) correlated to the increases in psychosis rating which is consistent with our previous reported correlation between altered membrane fluidity and the severity of symptomatology. In addition, decreases in 18:2 (n - 6) but not 20:4 (n - 6) was significantly correlated to the increases in psychosis rating. The present results lend further support that decreased levels of RBC PUFAs in schizophrenic patients lie in an initial stage of PUFAs pathway, possibly a defective uptake of 18:2 (n - 6) into RBC membranes.