Genetic configurations resulting in high ratios of p-tubulin to a-tubulin are toxic in S. cerevisiae, causing microtubule disassembly and cell death. We identified three non-tubulin yeast genes that, when overexpressed, rescue cells from excess p-tubulin. One, RBL2, rescues p-tubulin lethality as efficiently as does a-tubulin. Rbl2p binds to p-tubulin in vivo. Deficiencies or excesses of either Rbl2p o~ a-tubulin affect microtubuledependent functions in a parallel fashion. Rbl2p has functional homology with murine cofactor A, a protein important for in vitro assays of p-tubulin folding. The results suggest that Rbl2p participates in microtubule morphogenesis but not in the assembled polymer.