Abstract Beta-cryptoxanthin (β-Crp), a mono-hydroxylated β-carotene, is a major dietary provitamin A xanthophyll. The immunostimulatory effect of β-Crp was examined using human hybridoma HB4C5 cells and mouse primary lymphocytes in vitro and using mice in vivo. IgM production by the HB4C5 cells and both IgA and IgG productions by mouse primary lymphocytes from mesenteric lymph node and spleen were accelerated in vitro by the treatment of β-Crp in dose-dependent manners. Afterwards 6-week-old female BALB/c mice were administered with a low or high dose of β-Crp for 14days, mesenteric lymph node and spleen were excised and the immunoglobulin production levels were evaluated using lymphocytes from mesenteric lymph node and spleen in vivo. Results exhibited that all of IgA, IgG, and IgM productions by lymphocytes from mesenteric lymph node were increased. Especially, the IgG production increased with statistically significant differences in both of the low and high dose groups against the control group. The immunostimulatory effect on splenocytes was also observed although not as clear as on lymphocytes from mesenteric lymph node. Overall results suggest that β-Crp may stimulate the humoral immunity in mammals. Hence, β-Crp might have a potentially significant impact on human health and on prevention of diseases.