This study was undertaken to determine whether the large delayed creatine kinase (CK) rise, previously only reported in normal subjects after stepping exercise, was caused by the eccentric or concentric contractions. On separate occasions, five normal subjects performed the same amount of total work by walking either up (mainly concentric contractions) or down (mainly eccentric contractions) a treadmill inclined at 13 degrees. After uphill walking, peak plasma CK values of 60-200 IU/liter occurred 24 hours after exercise. Downhill walking resulted in peak values of 700-1500 IU/liter 4-7 days later. It is concluded that it is the eccentric contractions that are responsible for the large enzyme efflux.