The major flavin reductase from Vibrio fischeri, FRase I, has been crystallized in the presence of FMN by the vapor diffusion method using polyethylene glycol 4000 as a precipitant. The crystals belonged to the monoclinic space group C2 with unit cell dimensions, a = 101.6 A, b = 63.2 A, c = 74.4 A, and beta = 100.0 degrees. The crystals are expected to contain two FRase I molecules per asymmetric unit. The crystals diffracted X-rays to at least 2.2 A resolution and are appropriate for structural analysis at high resolution.