Five infants had interstitial pneumonitis with constant histologic findings, which was different from that previously described in children. All the infants presented with tachypnea at birth and persistent disease, both clinically and radiographically, despite treatment. Open-lung biopsy in each case showed a diffuse interstitial thickening due to pale oval and spindle-shaped histiocytes without scarring. This neonatal cellular interstitial pneumonitis differs both clinically and histologically from the usual interstitial pneumonitis, lymphocytic interstitial pneumonitis and desquamative interstitial pneumonitis observed in adults and children. The etiology of this cellular interstitial pneumonitis in neonates is unknown.