The Q-rich domain of the mouse sex determining gene, Sry, is encoded by an in-frame insertion of a repetitive sequence composed of mostly CAG repeats. The exact function of this Q-rich domain is unknown. Studies on the polymorphisms within this Q-rich domain among different domesticus and musculus mouse strains suggest a possible role for this domain in sex determination. Using the farwestern protein-blotting technique and recombinant fusion proteins containing the Sry Q-rich domain as probes, three Sry interactive proteins of 94, 32 and 28 kDa apparent molecular weight (Sip-1, -2 and -3 respectively) were consistently detected in adult testis. Sip expression was detected in somatic cells and was associated with the spermatogenic activity of the testis. During embryogenesis, Sips were readily detected in total tissue extracts of embryos as early as E8.5 day. In fetal gonads of both sexes, their expression peaked around E11.5-13.5 day, at the time of sex determination and differentiation, and decreased drastically towards late stages of gestation. These observations support the hypothesis that the Q-rich domain may contribute to the biological function(s) of mouse Sry through a protein-protein interactive role(s).