Aims-To study the correlations between total vitamin B-12(B-12), holo-haptocorrin, and holo-transcobalamin II (holo-TCII) concentrations in human sera; the association between reduced holo-TCII concentrations and macrocytosis attributable to B-12 deficiency. Methods-Serum samples from 38 healthy volunteers, 113 patients with normal total serum B-12 concentrations and 93 patients with low total serum B-12 were studied. Holo-TCII was removed from whole serum by adsorption with amorphous precipitated silica, and both whole serum and adsorbed serum were assayed for B-12 using the Becton Dickinson vitamin B-12 [Co-57] radioassay kit. Results-In all three groups of subjects studied there were strong correlations between the logarithms of the total serum B-12 and the holo-haptocorrin concentrations with regression coefficients between 0.884 and 0.967. By contrast, the correlations between the logarithms of the total serum B-12 and holo-TCII concentrations were weaker, especially in the patients with normal or low total serum B-12 for whom the regression coefficients were 0.491 and 0.391, respectively. Analysis of the clinical records of a proportion of the patients studied indicated that there were many more patients with low holo-TCII concentrations than with haematological disturbances related to B-12 deficiency. Conclusions-The total serum B-12 concentration is a relatively poor indicator of holo-TCII concentrations and, therefore, of the ability of serum to deliver B-12 to tissues. Additional information regarding B-12 values can therefore be gleaned from measuring holo-TCII concentrations in the serum. Low holo-TCII concentrations, however, are an early sign of negative B-12 balance and are frequently unassociated with haematological abnormalities caused by B-12 deficiency.