In 3 experiments, the authors examined the role of knowledge activation in the suppression of contextually irrelevant meanings for ambiguous homographs. In Experiments 1 and 2, participants with greater baseball knowledge, regardless of reading skill, more quickly suppressed the irrelevant meaning of ambiguous words in baseball-related, but not general-topic, sentences. Experiment 3 demonstrated that participants with greater general knowledge, regardless of reading skill, more quickly suppressed the irrelevant meaning of the ambiguous words in general-topic sentences. As predicted by D. S. McNamara's (1997) knowledge-based account of suppression, ambiguity effects are influenced by greater activation of knowledge related to the intended meaning of the homograph. These results challenge inhibition (e.g. M. A. Gernsbacher, K. R. Varner. & M. Faust, 1990) as the sole mechanism responsible for the suppression of irrelevant information.