A second randomized double-blind study to determine the efficacy of doxycycline, 100 mg daily, for the prevention of travelers' diarrhea was carried out among 50 Peace Corps Volunteers during their first 10 wk in Morocco. The volunteers took either doxycycline or placebo for 3 wk, and were observed for an additional 7 wk. Eleven of 24 taking the placebo and 2 of 26 taking doxycycline had travelers' diarrhea during the treatment period (P less than 0.01). One week after cessation of the doxycycline, however, persons in that group developed an increase in frequency of travelers' diarrhea (P less than 0.05) so that by 3 wk after the drug was stopped, there were no differences between groups. Enterotoxigenic E. coli, most of which were sensitive to doxycycline, were the most frequently isolated pathogens during the entire study. This study corroborates the effectiveness of doxycycline prophylaxis for travelers' diarrhea.