OBJECTIVE: To determine if 35 days of creatine supplementation (Cr) followed by 28 days of no supplementation altered lower leg anterior compartment pressure (ACP) at rest and after exercise. DESIGN AND SETTING: Subjects were divided into 2 treatment groups: (1) high dose (0.3 g Cr.kg body mass(-1).d(-1) for 7 days followed by 0.03 g Cr.kg body mass(-1).d(-1) for 28 days), or (2) low dose (0.03 g Cr.kg body mass(-1).d(-1) for 35 days). After 35 days, supplementation was terminated, and no Cr was ingested for 28 days. SUBJECTS: Sixteen physically active, healthy, college-aged males (O(2)max = 47.6 +/- 5.1 mL.kg(-1).min(-1)). MEASUREMENTS: At baseline, 7 days and 35 days of supplementation, and 28 days postsupplementation, ACP was measured preexercise and immediately, 1, 5, 10, and 15 minutes postexercise after a treadmill run at 80% O(2)max. RESULTS: For ACP, there was no significant group-by-time interaction, but there was a significant time effect for group when the data were combined. ACP was significantly increased at preexercise, immediately postexercise, and 1, 5, and 10 minutes from baseline to 7 days. ACP remained significantly elevated from baseline at 35 days immediately postexercise and 1 minute postexercise. After 28 days of no supplementation, ACP began to return to presupplementation levels, with only the 1-minute postexercise measurement significantly elevated from baseline. CONCLUSIONS: Creatine supplementation increased ACP at rest and after exercise, and ACP began to return to normal after 28 days of no supplementation.