The effect of colchicine on the mating reaction in Chlamydomonas moewusii was investigated. Five mM colchicine was found to cause a 96% inhibition of gamete fusion, without disrupting the preceding agglutination reaction or cell motility. Electron microscope examination of colchicine-treated gametes revealed a 98% inhibition of mating structure activation, suggesting that the drug had rendered the gametes incapable of generating and/or responding to the signal for mating structure activation which normally accompanies sexual agglutination. Light microscope analysis revealed that flagella of adhering drug-treated cells entwined loosely so that treated gametes were unable to establish the flagella tip alignment, and contact between partners' anteriors which facilitates cell fusion in control gametes. The misalignment of colchicine-treated cells is thought to result from a drug induced disruption of the tipping reaction. A model for the colchicine-labile system responsible for tipping is proposed.