Abstract Tetrandrine and berbamine are two naturally occuring analogues with a bis-benzylisoquinoline structure. Comparative in vitro studies show that tetrandrine has significantly greater suppressive effects on adherence, locomotion and 3H-deoxyglucose uptake of neutrophils, as well as the mitogen-induced lymphocyte responses and mixed lymphocyte reactions. Also, tetrandrine displayed anti-oxidant activity while berbamine did not. By contrast, berbamine demonstrated a significantly greater capacity for inhibition of NK cell cytotoxicity. These results show that tetrandrine is superior to berbamine in most aspects of anti-inflammatory and immunosuppressive activity. Since these two alkaloids differ by only one substitution in the side chain of one of the benzene rings, these findings may provide further insight into structure — activity relationships and clues to the synthesis and development of active analogues of this promising class of drugs for the treatment of chronic inflammatory diseases.