To determine the significance of the commonly observed fall in serum vitamin B-12 levels during pregnancy, serum levels of the B-12 metabolites methylmalonic acid (MMA) and homocysteine (Hey) were measured in a group of 50 pregnant patients with subnormal serum B-12 (range 45-199 pg/ml) and the results compared with those of 25 pregnant controls (serum B-12 208-580 pg/ml), Mean values for serum MMA and total Hey in the subnormal B-12 group were 445.4 nmol/L and 7.03 mu mol/L, respectively, which were not significantly different from the mean MMA of 440.5 nmol/L and Hey of 6.88 nmol/L in the controls, For the total group of patients, neither serum MMA nor serum Hey levels correlated with serum B-12. One-third of pregnant patients showed elevated serum MMA values, independent of B-12 status, Significant elevation of serum Hey was detected in only two patients, both with subnormal serum B-12 and hematological evidence of B-12 deficiency, We conclude that the usual fall in serum B-12 concentration in pregnancy does not reflect B-12 deficiency at the biochemical level, In establishing true B-12 deficiency in pregnancy, the serum Hey level (in the absence of folate deficiency) but not serum MMA, is of value. (C) 1995 Wiley-Liss, Inc.