The effect of inhibition of nitric oxide production on sweating rate (SR) and on core, rectal, and tail skin temperatures was measured in five Thoroughbred horses during exercise of variable intensity on a high-speed treadmill. A standard exercise test consisting of three canters [approximately 55% maximum O2 uptake (VO2max)], with walking (approximately 9% VO2max) and trotting (approximately 22% VO2max) between each canter, was performed twice (control or test), in random order, by each horse. N(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg), a competitive inhibitor of nitric oxide synthase, was infused into the central circulation and induced a significant reduction in the SR measured on the neck (31.6 +/- 6.4 vs. 9.7 +/- 4.2 g x min(1) x m(-2); 69%) and rump (14.7 +/- 5.2 vs. 4.8 +/- 1.6 g x min(-1) x m(-2); 67%) of the horses during canter (P < 0.05). Significant increases in core, rectal, and tail skin temperatures were also measured (P < 0.05). L-Arginine (200 mg/kg iv) partially reversed the inhibitory effects of L-NAME on SR, but core, rectal, and tail skin temperatures continued to increase (P < 0.05), suggesting a cumulation of body heat. The results support the contention that nitric oxide synthase inhibition diminishes SR, resulting in elevated core and peripheral temperatures leading to deranged thermoregulation during exercise. The inhibition of sweating by L-NAME may be related to peripheral vasoconstriction but may also involve the neurogenic control of sweating.