Astaxanthin, a carotenoid without provitamin A activity, enhances murine T-helper (Th) cell clone-mediated antibody (Ab) production with suboptimal antigen (Ag) challenges. It also suppresses interferon-γ (IFN-γ) production by cloned murine Th1 cells. β-Carotene is less effective than astaxanthin. This study evaluates the effects of various carotenoids with various relative polarity, provitamin A activity, and antioxidant activity. Carotenoids tested include astaxanthin, cantaxanthin, zeaxanthin, lutein, and lycopene, and their effects were tested at a concentration at which astaxanthin's effect was most potent. A.E7 and CDC35 cells are used as representative type 1 and type 2 Th cell (Th1 and Th2) clones, respectively. In the Th1 clone, astaxanthin, but not other carotenoids, suppressed IFN-γ production and increased the number of Ab-secreting cells with the use of primed spleen cells. With cultures of Th1 cells and unprimed spleen cells, astaxanthin and zeaxanthin augmented the number of immunoglobulin M Ab-secreting cells. In the cultures of Th2 clone and primed spleen cells, astaxanthin, but not other carotenoids, enhanced the number of Ab-.secreting cells. With unprimed spleen cells, lycopene suppressed Th2 clone-mediated Ab production. Interleukin-5 production by the Th2 clone was not significantly altered with the carotenoids tested, irrespective of the use of unprimed or primed spleen cells. Carotenoid actions on Th cells may vary in each carotenoid and do not seem to be closely associated with carotenoid antioxidant activity or relative polarity.