Reported residential fungal contamination has been associated consistently with increased symptoms among occupants; however, an objective measure of a health effect is lacking, and a pathophysiologic mechanism has not been established. Our objective was to determine if exposure to indoor fungal contamination influenced T-cell differentiation. In this study, we contrasted lymphocyte populations, measured by flow cytometry, between a group of children who lived in homes with considerable fungal contamination (n = 39) and a group in less-contaminated homes (n = 20). Indicators of fungal biomass were viable fungi in house dust and air ergosterol in the child's bedroom. Living in a more-contaminated home versus a less-contaminated home was associated with a larger number of CD3+ T cells expressing CD45RO (1.5 x 10(9)/I versus 1.1 x 10(9)/I, respectively; p = .05, two-tailed t testing) and a reduced CD4/CD8 ratio (1.6 versus 1.8, respectively; p = .04). The differences persisted over a 12-mo period, and they were not explained by the child's age or total serum IgE, dust mite antigens, and the presence of furry or feathered pets or a humidifier. The results suggest that residential fungal contamination leads to chronic stimulation of children's lymphocytes.