Of 247 patients referred to the Pediatric Immunology Clinic, University of Connecticut Health Center, Farmington, Conn., for recurrent infections, 13 patients were found to have an abnormal delay in the onset of IgG synthesis and prolongation of the physiologic hypogammaglobulinemia of infancy. At first observation, their mean age was 10.6 months. All patients had abnormally low serum IgG levels (≤2 SD for their age). The mean serum IgG level for our patient population was 270 ± 81 mg/dl; the mean serum IgG level of the control group was 749 ± 440 mg/dl. Clinically, these patients were first observed with recurrent otitis media, respiratory infections, bronchitis and/or asthma, and formula intolerance. Despite recurrent respiratory tract infections, specific antibodies to the respiratory viruses were absent in nine of 11 patients tested who were observed before 17 months of age. On follow-up, two of the 13 patients never developed specific antibodies to viral agents, although their serum IgG levels normalized; one patient became serology positive at the same time that the serum IgG normalized. In two patients, the serum IgG levels returned to within the normal range for age before the appearance of specific viral antibodies. In eight patients, the appearance of specific viral antibodies was detected before the serum IgG levels returned to normal. Five of these eight patients were treated for short periods (9 months) with replacement immune serum globulin (intramuscular) therapy and did clinically well. These observations suggest that replacement immune serum globulin for short periods of time does not appear to suppress the production of specific, naturally occurring antibodies and the resolution of the hypogammaglobulinemia. © 1990.