Twenty college‐age males participated in a weight‐training experiment, three sets of 10 repetitions at 70% one repetition maximum (1 RM) for the squat, to examine the time course relationship between prostaglandin (PG) formation, creatine kinase (CK) activity, and ratings of perceived soreness (RPS). Two groups of 10 each received aspirin (3 g/day) or placebo for 4 consecutive days, starting 1 day prior to workout. There was no significant difference between the groups for CK and RPS during the course of the experiment, but the PG values were significantly different (p<0.05) between groups at all time points measured. Changes observed in biochemical parameters followed an exponential growth and decay during the period following exercise for all variables. The 24 hour PG level was significantly higher(p<0.05) than the pre‐and postexercise and 72 hour levels, but not significantly different from the 48 hour level. Ratings of soreness were not significantly different at the 24 and 48 hour intervals, but both were significantly higher at all other time intervals. The mean CK activity at the 24 and 48 hour intervals was not significantly different, but the 24 hour serum CK activity was significantly higher (p<0.05) than the other time intervals. In conclusion, PGs do not seem to have any significant effect on the CK activity nor on the delayed onset of muscle soreness. However, given the small sample and interindividual variations, further investigation concerning the role of PGs on delayed onset of muscle soreness should be conducted.