Previous studies have shown that schizophrenics, in comparison to controls, have reduced cortical spine density and smaller striatal spines. The current study in the rat was conducted to determine whether such differences could result from chronic neuroleptic treatment and whether they are correlated with neuroleptic-induced oral dyskinesias. Rats administered 1.5 mg/kg/day of haloperidol (HA) (n = 28) or water (n = 10) were tested for vacuous chewing movements (VCMs). After 6 months, rats were divided into low and high VCM groups; all but seven high VCM rats were sacrificed. These rats (withdrawn group) were withdrawn from HA for 4 weeks. Random electron micrographs of the striatum were analyzed for spine changes. Spine size was not significantly affected by HA (0.193 vs 0.174 microm2, HA and control, respectively) nor correlated with oral dyskinesias (0.191 vs 0.196 microm2, low and high VCM groups, respectively). These results suggest that smaller spines in schizophrenic striatum may be correlated with the disease rather than caused by neuroleptic treatment. Spine density decreased in the HA-treated group (32.7 +/- 9.5) in comparison to controls (53.7 +/- 7.3, P < 0.001) and remained low in the withdrawn group (35.0 +/- 4.2, P < 0.01). Spine density also decreased in both the low (37.3 +/- 9.9, P < 0.01) and the high (28.0 +/- 7.0, P < 0.000) VCM groups in comparison to controls. However, there was no significant difference between high and low VCM groups, suggesting that decreased spine density is independent of oral dyskinesias. These results suggest that the decreased spine density observed in schizophrenic cortex may be a result of neuroleptic treatment.