Increasingly, humans are exposed to drug/chemical mixtures. These exposures can result from therapeutic interventions or environmental sources. Of interest is the interaction that may occur among the components of these mixtures. Since interaction can be dose-dependent, it is important to determine exposure levels to either exploit the benefits of the interaction in a therapeutic application or to avoid the effect of the interaction in the case of an environmental risk assessment. We propose generalized linear models that permit the estimation of interaction threshold boundaries. The methods developed are applied to the combination of ethanol and chloral hydrate. Copyright © 2005 John Wiley & Sons, Ltd.