A concise but critical review of the literature on the immunological aspects of sickle cell syndrome (SCS) was carried out. This exercise revealed our poor understanding of the immune status of these persons, while most of them succumb to overwhelming infections. We used laser nephelometric technique to quantitate the C4. Unlike the serum IgM complex, we found that IgG and IgM were raised in these persons. However, a significant rise in serum IgM was noted during the symptom of vaso-occlusive painful crisis. The profile of complement protein consumption correlated positively with the levels of the immune complexes. We suggest that sickle cell persons are generally more susceptible to immune complex pathology and the possible contribution of IgM to the symptom of vaso-occlusive painful crisis was discussed.