Signal transducer and activator of transcription 6 (STAT6) regulates transcriptional activation in response to interleukin-4 (IL-4) by direct interaction with coactivators. Among them, NCoA-1, a member of the p160/steroid receptor coactivator (SRC) family, has been found to bind to STAT6 with the region B of its putative Per-Arnt-Sim (PAS) domain. STAT6 interacts specifically with NCoA-1 via an LXXLL motif in its transactivation domain. Crystals of the NCoA-1(257-385) domain in complex with the STAT6(794-814) LXXLL motif were obtained in two hexagonal space groups. The crystals in space group P6(1), with unit-cell parameters a = 61.7, b = 61.7, c = 146.5 A, alpha = beta = 90, gamma = 120 degrees, diffract to 2.8 A at a home source. Crystals belonging to space group P6(2), with unit-cell parameters a = 62.0, b = 62.0, c = 73.6 A, alpha = beta = 90, gamma = 120 degrees, diffract to 1.8 A at a synchrotron source.