The effect of complete Freunds Adjuvant (CFA) has been investigated on the multi-low-dose streptozotocin (STZ) model of diabetes in mice of the H-2b (C57Bl/6) and of the H-2k (A/J, CBA) genotypes. Physiological (glycemia and body weight) and morphological (insulitis) parameters were monitored. STZ was used at standard and sub-diabetogenic dose levels (45 and 22.5 mg/kg STZ, for five consecutive days respectively) and CFA was given as a single dose (0.1 ml) on the first dosage day. In H-2k mice, CFA was synergistic with STZ at 45 mg/kg but did not cause the 22.5 mg/kg dose to raise glycemia to diabetic levels. By comparison, CFA was not synergistic with STZ at 45 mg/kg in H-2b mice, but did convert the subdiabetogenic dose to a diabetogenic action in these animals. Histologically, it was noted that insulitis was a more prominent and persistent feature of the H-2k mice. It occurred at the subdiabetogenic dose level of STZ in H-2k mice, in the absence of increased glycemia, suggesting that these two phenomena are not related. CFA, either alone, or with STZ, caused severe persistent perilobular inflammation of the exocrine pancreas. It did not increase the incidence or severity of insulitis. A possible mechanism whereby CFA is synergistic with STZ at different doses in H-2b and H-2k mice is suggested.