The study investigated the hypothesis that three consecutive days of prolonged cycle exercise would result in a sustained reduction in the Ca2+-cycling properties of the vastus lateralis in the absence of changes in the sarcoplasmic (endoplasmic) reticulum Ca2+-ATPase (SERCA) protein. Tissue samples were obtained at preexercise (Pre) and postexercise (Post) on day 1 (E1) and day 3 (E3) and during recovery day 1 (R1), day 2 (R2), and day 3 (R3) in 12 active but untrained volunteers (age 19.2 +/- 0.27 yr; mean +/- SE) and analyzed. for changes (nmol.mg protein(-1). min(-1)) in maximal Ca2+ -ATPase activity (V-max, Ca2+ uptake and Ca2+ release (phase 1 and phase 2), and SERCA isoform expression (SERCA1a and SERCA2a). At E1, reductions (P < 0.05) from Pre to Post in V-max (150 +/- 7 vs. 121 +/- 7), Ca2+ uptake (7.79 +/- 0.28 vs. 5.71 +/- 0.33), and both phases of Ca2+ release (phase 1, 20.3 +/- 1.3 vs. 15.2 +/- 1. 1; phase 2, 7.70 +/- 0.60 vs. 4.99 +/- 0.48) were found. In contrast to V-max, which recovered at Pre E3 and then remained stable at Post E3 and throughout recovery, Ca2+ uptake remained depressed (P < 0.05) at E3 Pre and Post and at RI as did phase 2 of Ca2+ release. Exercise resulted in an increase (P < 0.05) in SERCA1a (14% at R2) but not SERCA2a. It is concluded that rapidly adapting mechanisms protect V-max following the onset of regular exercise but not Ca2+ uptake and Ca2+ release.