A survey of 1659 households in a periurban community in Mexico City was carried out to assess the frequency of and risk factors for inappropriate antimicrobial therapy in acute diarrhea. The housewife was interviewed to obtain information of the occurrence of diarrhea or use of an antibiotic in the previous 2 weeks by any member of the family. An antibiotic was used in 37% or 287 diarrheal episodes although only in 5% of all episodes was this therapy indicated, based on the presence of gross blood in stools. Patients seen by a physician were 6 times more likely to be treated with an antibiotic compared to those who did not consult a physician (p < 0.001). Self-medication was associated with a higher risk of using an inadequate drug or dose (in 72% of treated episodes) and of following treatment for less than 5 days (in 66% of treated episodes). Other risk factors significantly and independently associated with antibiotic misuse were: an increased number of stools (odds ratio [OR] = 1.21; 95% confidence interval [CI] = 1.04, 1.41), bloody diarrhea (OR = 19.04; 95% CI = 2.52, 160.90) and family crowding (OR = 2.07; 95% CI = 1.17, 3.63). These findings support future community-oriented educational interventions aimed at improving physician prescribing practices and patient compliance behavior in order to achieve a more rational use of antibiotics.