Sex-lethal (SXL) is an RNA binding protein that acts as a regulator of both alternative pre-mRNA splicing and translation. Because SXL must sometimes function at some distance from its binding sites, it is believed that it must interact with other proteins. We used a yeast two-hybrid screen to isolate a novel Drosophila protein, SIN (SXL interactor), that interacts specifically with SXL. A direct physical association was demonstrated in vitro, and a single SXL RNA binding domain was sufficient for the interaction. SIN shows a high degree of similarity to a mammalian protein of unknown function. The cytogenetic location of Sin is 78A2-4. The transcript, which is abundant in early embryos, appears to be of maternal origin.