The effects of caffeine (CF) dosage on physical performance and the impact of CF after exhaustion are poorly defined. We studied the effects of CF dosage on endurance of both non-fatigued and previously exhausted muscles in nine (7 male, 2 female) healthy, low CF consuming (CF intake 40 ± 11 mg/day; mean ± SE) soldiers (age 23 ± 2 yr; weight 79 ± 4 kg). Subjects performed 4 pairs of 2-leg constant work rate exercise tests isolated to the knee extensor muscles of each leg. One pair of dynamic knee extension (DKE) tests was performed each wk for 4 wks and order of test pair performance was random. The first of each pair of tests began with fresh (FRSH) muscles and the second test began after 1 hr rest from the point of exhaustion (EXH) of the first. For each subject, work rate was identical for all 8 tests. Test pairs (first-second) were: A) placebo (PL)-PL; B) 2.5 mg/kg b. w. (lower dose, LDCF)-PL; C) 5.0 mg/kg b. w. (higher dose, HDCF)-PL; D) PL-HDCF, CF and PL capsules were taken double-blinded 1 hr prior to each DKE test. Findings for endurance time (sec) were: When FRSH, endurance time was approximately 40 to 50% longer (P < 0.05) for DKE during both LDCF and HDCF than during PL conditions and similar (P > 0.05) for LDCF and HDCF. After EXH, endurance time was 75% longer (P < 0.05) for DKE during PL after HDCF than for DKE during PL after PL conditions. Endurance time was shorter for PL after LDCF (P < 0.05) than for LDCF when FRSH. However, endurance time for PL following HDCF was similar (P > 0.05) to that for HDCF when FRSH. Thus, when FRSH, LDCF substantially increased DKE endurance with no further benefit from HDCF. However, after EXH, earlier ingestion of HDCF but not LDCF markedly increased endurance. We conclude that, for nonfatigued muscles, DKE endurance is optimally improved by lower doses of caffeine and that higher doses of caffeine are needed to optimize endurance of previously exhausted muscles.Table