Seven patients with MP and four controls were injected with 0.04 to 0.05 microgram of [57Co] cyanocobalamin i.m. or i.v. in order to study the shift of binding with time and the conversion of one Cbl to another. The initial pattern of binding reflected the proportion of the apo forms of TC II and R binders. In MP there was more initial binding of the injected Cbl to R-type binders and less to TC II. During the first 48 hr after intake, the injected Cbl remained mostly as cyanocobalamin. Some adenosylcobalamin appeared transiently in both control and MP subjects. Radioactive methylcobalamin did not appear in the circulation until after 48 hr, and the conversion of cyanocobalamin to methylcobalamin within the circulation was greater in MP subjects. Serum from some subjects converted small amounts of cyanocobalamin to all other forms in vitro by a heat-stable, extracellular property which was abolished by dialysis of the serum. This property of serum could have accounted for the early conversion to adenosylcobalamin but not, at least as an in vitro phenomenon, to the late appearance of methylcobalamin. Although the expected increases and abnormal patterns of R binders were observed in MP, these abnormalities could not be correlated with the increased conversion to plasma methylcobalamin. During the first 6 hr after injection the R binder-Cbl designated as alpha 2-R-Cbl disappeared from the circulation at a rate faster than that of alpha 1-R-Cbl. Subsequently the alpha 2 and alpha 1 components of R binder-Clb cleared at the same rate, and this rate was the same for both control and MP subjects.