WILLOUGHBY, D. S., and J. ROSENE. Effects of oral creatine and resistance training on myosin heavy chain expression. Med. Sci. Sports Exerc., Vol. 33, No. 10, 2001, pp. 1674–1681. Purpose: This study examined 12 wk of creatine (Cr) supplementation and heavy resistance training on muscle strength and myosin heavy chain (MHC) isoform mRNA and protein expression. Methods: Twenty-two untrained male subjects were randomly assigned to either a control (CON), placebo (PLC), or Cr (CRT) group in a double-blind fashion. Muscle biopsies were obtained before and after 12 wk of heavy resistance training. PLC and CRT trained thrice weekly using three sets of 6-8 repetitions at 85–90% 1-RM on the leg press, knee extension, and knee curl exercises. CRT ingested 6 g·d−1 of Cr for 12 wk, whereas PLC consumed the equal concentration of placebo. Results: There were no significant differences for percent body fat (P > 0.05). However, for total body mass, fat-free mass, thigh volume, muscle strength, and myofibrillar protein, CRT and PLC exhibited significant increases after training when compared to CON (P < 0.05), whereas CRT was also significantly greater than PLC (P < 0.05). For Type I, IIa, and IIx MHC mRNA expression, CRT was significantly greater than CON and PLC, whereas PLC was greater than CON (P < 0.05). For MHC protein expression, CRT was significantly greater than CON and PLC for Type I and IIx (P < 0.05) but was equal to PLC for IIa. Conclusion: Long-term Cr supplementation increases muscle strength and size, possibly as a result of increased MHC synthesis.