We examined the development of skin test reactivity and clinical allergen sensitivity in infancy. Seventy-eight infants of atopic parents were skin prick tested every 4 mo from 4 to 16 mo and an additional 57 of these infants were tested at 20 mo. Wheal diameters were recorded for histamine (1 mg/ml) and specific allergen reactions by use of cow's milk, egg albumen, wheat, and Dermatophagoides pteronyssinus. The histamine mean wheal diameter was significantly lower at 4 and 8 mo compared to the older infants. Infants at 20 mo also had significantly smaller wheals than adult controls. Histamine reactivity was greater in atopic infants at 4 mo compared to nonatopic infants. Reactions to ingested allergens occurred early in infancy but were usually transient. There was a good correlation between skin sensitivity and clinical immediate-food hypersensitivity to the food concerned. In contrast, reactions to the inhaled allergen, D. pteronyssinus, occurred later in infancy, were persistent, and increased in size with age. Although we found no relationship between the acquisition of skin reactivity to D. pteronyssinus and development of the respiratory symptoms of atopic disease during the period of the study, it is possible that inhaled allergen reactivity may be related to respiratory symptoms at later ages. Despite the decreased histamine reactivity in early infancy, skin tests proved reliable markers of clinical disease in ingested but not inhalant allergen sensitivity.