AIMS: To compare the efficacy of sublingual and oral administration of 500 micro g of cobalamin in subjects with cobalamin deficiency. MATERIALS AND RESULTS: Thirty subjects with low serum concentrations of cobalamin participated in the study. Subjects were randomly allocated to receive one tablet daily of 500 micro g cobalamin sublingually or orally, or two tablets daily of a vitamin B complex. Serum cobalamin concentrations before treatment were 94 +/- 30 pmol l-1, 108 +/- 17 pmol l-1 and 98 +/- 14 pmol l-1 in the sublingual B12, oral B12 and oral B-complex groups, respectively. After 4 weeks, concentrations rose to 288 +/- 74 pmol l-1, 286 +/- 87 pmol l-1 and 293 +/- 78 pmol l-1, respectively. The increase in each group across time was statistically significant (P = 0.0001, differences [95% confidence intervals] 194.2 (114.5, 273.9), 178.3 (104.2, 252.4), and 195.1 (135.0, 255.2) pmol l-1, respectively). There was no significant difference in concentrations between the treatment groups. CONCLUSION: A dose of 500 micro g of cobalamin given either sublingually or orally is effective in correcting cobalamin deficiency.