The proportion of diarrheal illnesses of unknown origin that were associated with small round virus (SRV, 23-38 nm) particles among children less than 2 years old attending an outpatient clinic in Baltimore was determined. During a 9-month period, stool specimens from 188 patients with acute diarrhea and 108 healthy age-matched control children were examined for enteric bacterial pathogens, protozoa, enteric adenovirus, and rotavirus. An enteropathogen was identified in 75 patients (40%) and in 21 controls (20%). A random sample of specimens without an identifiable pathogen was then examined for SRV particles by immune electron microscopy (IEM) using commercial human gamma globulin. Viruses of 26-30 nm diameter that were not enteroviruses were detected in specimens from 9 (12.5%) of the 72 patients and 1 (1.8%) of the 53 control subjects (P less than .04). Of 6 patients with available acute and convalescent sera, 4 demonstrated a significant immune response when tested by IEM. All patients experienced a mild, self-limited (1-3 days) illness. These findings suggest that SRV may be endemic in the Baltimore community and may result in clinically significant diarrheal illnesses.