Systemic injections of nitric oxide synthase (NOS) inhibitors have been shown to decrease exploratory behaviour and to induce catalepsy in a dose-dependent manner in male albino-Swiss mice. This effect may be related to motor impairments since these drugs can induce catalepsy in rodents. The objectives of these exeriments was to compare the effects of two NOS inhibitors in mice in tests aimed to investigate exploratory behaviour and to assess motor control. We also investigated if these effects were centrally mediated. The acute effects of the NOS inhibitors NG-nitro-L-arginine (L-NOARG, 10-80 mg/kg i.p.) and 7-nitroindazole (7-NIO, 3-30 mg/kg i.p.) on exploratory activity were analysed in an open field arena. Drug effects on catalepsy were examined in the hanging-bar and wire-ring test. Footprint pattern after treatment with the two NOS inhibitors was evaluated and the results compared with those obtained with the dopamine D2 receptor antagonist Haloperidol (1-2 mg/kg i.p.). Sub-chronic (twice a day for 4 days) effects of L-NOARG (40 mg/kg) or 7-NIO (30 mg/kg) were also tested in the open field arena and catalepsy test. For i.c.v. injection mice were anesthetized with 2.5% 2,2,2-tribromoethanol (250 mg/kg, i.p.) and fixed in a stereotaxic frame. A stainless steel guide cannula (0.7 mm OD) was implanted aimed at the right lateral ventricle (coordinates:AP= -1.0 mm from bregma, L= 1.6 mm, D=3.5 mm). L-NOARG and 7-NIO decreased locomotion and rearing in the open field arena. Both drugs induced catalepsy in the hanging-bar test but did not change footprint pattern. The cataleptic effect of L-NOARG in the hanging bar and wire-ring tests were highly correlated (r=0.927). Similar effects were found after intracerebroventricular (i.c.v.) injection of L-NOARG (50-200 nmol) or NG-nitro-L-arginine methylester (L-NAME, 100-200 nmol). The exploratory and cataleptic effects of L-NOARG and 7-NIO provided evidence for tolerance after sub-chronic treatment. These results confirm that inhibition of neuronal NO formation induces impairment of exploratory behaviour. This effect does not seem to involve aspects evaluated by footprint analysis, such as weight support, trunk stability and foot placement. They could, however, be related to drug-induced catalepsy. These results suggest that interference with the striatal formation of nitric oxide may induce significant motor effects in mice.