The purposes of this investigation were first to determine the impact of 3 different creatine (Cr) loading procedures on skeletal muscle total Cr (TCr) accumulation and, second, to evaluate the effectiveness of 2 maintenance regimes on retaining intramuscular TCr stores, in the 6 weeks following a 5-day Cr loading program (20 g x day(-1). Eighteen physically active male subjects were divided into 3 equal groups and administered either: (a) Cr (4 x 5 g x day(-1) x 5 days), (b) Glucose+Cr (1 g x (-1) of body mass twice per day), or (c) Cr in conjunction with 60 min of daily muscular (repeated-sprint) exercise. Following the 5-day loading period, subjects were reassigned to 3 maintenance groups and ingested either 0 g x day(-1), 2 g. day(-1) or 5 g x day(-1) of Cr for a period of 6 weeks. Muscle biopsy samples (vastus lateralis) were taken pre- and post-loading as well as post-maintenance and analyzed for skeletal muscle ATP, phosphocreatine (PCr), Cr, and TCr concentrations. Twenty-four hour urine samples were collected for each of the loading days and last 2 maintenance days, and used to determine whole body Cr retention. Post-loading TCr stores were significantly (p <.05) increased in all treatment conditions. The Glucose+Cr condition produced a greater elevation (p <.05) in TCr concentrations (25%) than the Cr Only (16%) or Exercise+Cr (18%) groups. Following the maintenance period, muscle TCr stores were still similar to post-loading values for both the 2 g x day(-1) and 5 g x day(-1) conditions. Intramuscular TCr values for the 0 g x day(-1) condition were significantly lower than the other conditions after the 6-week period. Although not significantly different from pre-loading concentrations, muscle TCr for the 0 g x day(-1) group had not fully returned to baseline levels at 6 weeks post-loading. The data suggests that Glucose+Cr (but with a much smaller glucose intake than currently accepted) is potentially the most effective means of elevating TCr accumulation in human skeletal muscle. Furthermore, after 5 days of Cr loading, elevated muscle TCr concentrations can be maintained by the ingestion of small daily Cr doses (2-5 g) for a period of 6 weeks and that TCr concentrations may take longer than currently accepted to return to baseline values after such a Cr loading regime.