Phosphoinositide-specific phospholipase C-${gamma}1$ (PLC-${gamma}1$) is a pivotal mediator in the signal transduction cascades induced by many growth factors. Using a yeast two-hybrid system, heat-shock protein 90 (Hsp90) was identified as a PLC-${gamma}1$-binding protein. A co-immunoprecipitation experiment, using anti-PLC-${gamma}1$ antibody, demonstrated an in vivo interaction between Hsp90 and PLC-${gamma}1$ in the NIH-3T3 cells. The interaction in NIH-3T3 was unaffected by the PDGF treatment, inducing phosphorylation and activation of PLC-${gamma}1$. Direct interaction between Hsp90 and PLC-${gamma}1$ was confirmed by in vitro binding experiments using purified Hsp90 and PLC-${gamma}1$. Furthermore, Hsp90 increased the $PIP_2$-hydrolyzing activity of PLC-${gamma}1$ up to 2-fold at $0.1{mu}M$ in vitro. Taken together, we show for the first time, the interaction of PLC-${gamma}1$ with Hsp90, both in vivo and in vitro. We suggest that Hsp90 may play a role in PLC-${gamma}1$-mediated signal transduction.