To investigate the effects of low P50Hb on muscle capillarity, rats were injected with Na-cyanate (50 mg/kg BW) every day for 2 or 4 weeks (experimental). Controls received injections of saline. After 2 weeks P50 was reduced in the experimental animals (20.4 vs 30.3 Torr). After 4 weeks experimental animals showed a 13% increase in hematocrit and Hb. PVO2 was lower in experimental than in control rats (28.3 +/- 1.0 vs 33.8 +/- 4.7 mm Hg). Fiber cross-sectional area (FCSA), capillary density (CD) and capillary-to-fiber ratio (C/F) were measured in sections treated with the ATPase technique. FCSA was smaller in experimental than in controls (3000 +/- 491 vs 4121 +/- 415 micron 2 for the soleus and 3633 +/- 236 vs 4251 +/- 194 micron 2 for the gastrocnemius) and CD was higher (729 +/- 99 vs 578 +/- 75 cap/mm2 in the soleus and 388 +/- 19 vs 323 +/- 14 cap/mm2 in the gastrocnemius) but C/F was not different. Diffusion distances for O2 measured by the closest individual method were not significantly different between the two groups. The higher CD in the experimental animals seems to be the result of their smaller FCSA and not the result of capillary proliferation. The volume of tissue served by a capillary was significantly reduced in the experimental animals. This could help the transfer of O2 to the muscle in animals with a low P50 Hb.