Genetic configurations resulting in high ratios of beta-tubulin to alpha-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 beta-tubulin, One, RBL2, rescues beta-tubulin lethality as efficiently as does alpha-tubulin. Rbl2p binds to beta-tubulin in vivo, Deficiencies or excesses of either Rbl2p or alpha-tubulin affect microtubule-dependent functions in a parallel fashion, Rbl2p has functional homology with murine cofactor A, a protein important for in vitro assays of beta-tubulin folding. The results suggest that Rbl2p participates in microtubule morphogenesis but not in the assembled polymer.