Background TCR and CXCR4-mediated signaling appears to be reciprocally regulated pathways. TCR activation dampens the chemotactic response towards the CXCR4 ligand CXCL12, while T cells exposed to CXCL12 are less prone to subsequent TCR-activation. The heterotrimeric G proteins Gαq and Gαi2 have been implicated in CXCR4-signaling and we have recently also reported the possible involvement of Gαq in TCR-dependent activation of Lck (Ngai et al., Eur. J. Immunol., 2008, 38: 32083218). Here we examined the role of Gαq in migration and TCR activation. Results Pre-treatment of T cells with CXCL12 led to significantly reduced Lck Y394 phosphorylation upon TCR triggering indicating heterologous desensitization. We show that knockdown of Gαq significantly enhanced basal migration in T cells and reduced CXCL12-induced SHP-1 phosphorylation whereas Gαi2 knockdown inhibited CXCL12-induced migration. Conclusion Our data suggest that Gαi2 confers migration signals in the presence of CXCL12 whereas Gαq exerts a tonic inhibition on both basal and stimulated migrational responses. This is compatible with the notion that the level of Gαq activation contributes to determining the commitment of the T cell either to migration or activation through the TCR.