Although the study of the variation rules of the joint effects for multicomponent mixtures has gained increasing attention, it still remains unclear how the variation occurs and what the relationships between the joint effects of multicomponent mixtures and their corresponding binary mixtures are. To explain how the variation occurs, this study first proposes a hypothesis on the variation rules of the joint effects using the well-known transition state theory. The hypothesis concluded that the joint effect of multicomponent mixtures is among the joint effects of the corresponding binary mixtures. This hypothesis was named the fishing hypothesis because there is a similarity between the action process of the joint effects and the fishing process. Next, the hypothesis was validated by use of the experimental data by evaluating the joint effects of binary, ternary and quaternary mixtures containing cyanogenic toxicants and aldehydes on Photobacterium phosphoreum. The application of the fishing hypothesis can explain the rule as to how the joint effects of a multicomponent-mixture vary with its number of components and their ratios. This study provides a good method to predict the joint effects of multicomponent mixtures using the joint effects of their corresponding binary mixtures. An improvement in the fishing hypothesis will be needed in our future studies due to the approximate assumptions used in the deduction of the hypothesis (C) 2013 Elsevier B.V. All rights reserved.