To evaluate the field effectiveness of erythromycin prophylaxis for pertussis within families, a retrospective cohort study was conducted among 246 families. Overall 41% of the subjects (387 of 940) had been sick. The secondary attack rate was 65% for infants younger than 2 years, 54% for those 2 to 4 years old and 39% for children 5 to 9 years old, and it declined thereafter. The secondary attack rate decreased from 25% in families without prophylaxis to 17% in families with prophylaxis. The protection induced by prophylaxis did not vary with age or vaccination status. When prophylaxis was used before the onset of a secondary case, the secondary attack rate was 4% compared with 35% when given after a secondary case (P < 0.001). Erythromycin prophylaxis seems to be efficient in preventing secondary cases but is most useful when administered before the occurrence of the first secondary case.