Research suggests that dopamine may exert a neuromodulatory influence on automatic spreading activation within semantic networks. In order to investigate the influence of dopamine depletion on semantic activation in Parkinson's disease (PD), nine patients with PD performed a lexical decision task when on and off levodopa medication. Eleven healthy controls matched to the PD patients in terms of sex, age and education also participated in the study. Both directly related word pairs (e.g., tiger – stripe) and indirectly related word pairs (word pairs related via a mediating word, e.g., chalk – black) were used to measure semantic activation across stimulus onset asynchronies (SOAs) of 270msec, 520msec and 1020msec. Analysis of variance statistics revealed that the activation of directly related and indirectly related targets was slower for the PD group relative to the control group. Within group comparisons revealed further changes to semantic activation in PD patients off medication, with no activation of directly or indirectly related target words evident in PD patients off medication. These results further clarify the nature of dopamine's neuromodulatory influence on semantic activation, and suggest that the nature of altered semantic activation in PD may depend on the magnitude of dopamine depletion.