Cyclospora cayetanensis was detected in fecal specimens from 63 (1.1%) of 5,836 Peruvian children studied over 2 years; the protozoan was detected by modified acid-fast staining and autofluorescence under ultraviolet light. The highest prevalence occurred among children between 2 and 4 years of age. Thirty-two percent (20) of the 63 C. cayetanensis-infected children were symptomatic. Nineteen infected children were enrolled in a double-blind, placebo-controlled trial of a 3-day course of trimethoprim-sulfamethoxazole (TMP-SMZ; 5/25 mg/[kg·d]). Children were followed up with daily stool examinations (mean number of samples examined per child ± SE, 19 ± 4). The mean duration of oocyst excretion ± SE was 4.8 ± 1.2 days for TMP-SMZ recipients compared with 12.1 ± 6.1 days for placebo recipients (P < .02). The prevalence of C. cayetanensis infection decreases during winter months and as children age; it decreases precipitously by adulthood. In children in areas of endemicity, C. cayetanensis usually causes mild disease that is often asymptomatic. TMP-SMZ therapy significantly decreases the duration of oocyst excretion.