Selective homozygous deficiency of the second component of complement, C2, with increased susceptibility to infection was detected in five children of two unrelated families. Because the haemolytic activity of the alternative complement pathway (AP) was in the low normal range, we evaluated the AP activation pattern. Serum levels of factor B measured immunochemically and the haemolytic function of factor B were low normal. Levels of C3d were not increased. Activation products of factor B were undetectable indicating the absence of in vivo activation of AP. Activation of C3 in vitro by activators of the AP (zymosan A and lipopolysaccharide) was profoundly deficient in homozygous C2 deficiency while heterozygous carriers exhibited intermediate values. There was no correlation between serum levels of factor B and in vitro C3 activation. We conclude that defective AP activation may contribute to increased susceptibility to bacterial infections in some patients with homozygous C2 deficiency.