Two different strains of Ureaplasma urealyticum isolated in pure culture from the lungs of newborn human infants were shown to produce an acute, self-limiting, interstitial pneumonia in newborn C3H/HeN and C57BL/6 mice that were free of other respiratory pathogens. Lesion severity peaked 3 to 6 days following intranasal inoculation of ureaplasmas and was resolved by 12 days. Rhinitis and otitis also occurred but did so less frequently than pneumonia. Organisms were localized within the alveoli in areas of inflammation. In comparison with newborn mice, 14-day-old mice were less susceptible to either colonization or disease.