Opsonization of zymosan by plasma complement was studied in 12 consecutive patients with untreated, well-established Crohn's disease and in 12 healthy volunteers. Binding of C3b to zymosan was markedly increased in patients with Crohn's disease during the first 30 min of the alternative pathway reaction, whereas consumption of the native C3 protein was within the normal range in all patients. Our results are consistent with a decreased capacity for degradation of activated C3,C3b by the I-H factor inactivator system. This immunologic abnormality may contribute to a chronic activation of the complement sequence, previously demonstrated in Crohn's disease, and to a release of split products of inflammation-promoting character.