BACKGROUND: An allergic reaction with increased degranulation of mast cells has been suggested as a possible mechanism in sudden infant death syndrome (SIDS). STUDY DESIGN: Mast cell releasability was assessed in 2 study groups: A, 22 subjects, 16 first-degree relatives of infants who had had an apparent life-threatening event (ALTE) and 6 infants after ALTE and B, 46 first-degree relatives of SIDS cases. These groups were compared with 71 members of an age-matched control group. In each subject the skin wheal and flare reactions were measured after an intradermal injection of 0.02 mL of each of the following substances dissolved in phenol-saline solution: histamine 0.0001 mg/mL, histamine 0.001 mg/mL, codeine 0.5 mg/mL, codeine 1 mg/mL, compound 48/80 0.05 mg/mL, compound 48/80 0. 1 mg/mL, and phenol-saline solution. The size of wheal and flare skin reaction was assessed by computerized planimetry after the shape of the cutaneous response was copied onto a paper. RESULTS: The wheal and flare skin reaction to each of the substances was significantly larger in the 2 study groups compared with the control group (P <.05) except for the wheal reaction to compound 48/80 0.1 mg/mL, codeine 0.5 mg/mL, and histamine in both concentrations for group A and the wheal reaction to codeine 1 mg/mL and histamine in both concentrations for group B. All individuals with increased reaction belonged to 3 (50%) of 6 families with ALTE history and to 8 (73%) of 11 families with SIDS history. CONCLUSIONS: Increased mast cell hyper-releasability and degranulation take place in family members of some SIDS and ALTE cases and in some infants with ALTE, supporting a possible role for an immunologic mechanism in the pathophysiology of these entities.