• Phonological neighbourhood effects depend on target frequency in picture naming. • The frequency of phonological neighbours, less so their number, affects performance. • Phonological neighbours can both inhibit and facilitate picture naming. • An interactive activation model was used to simulate picture naming. • A slow rise in lexical activation is required to successfully simulate the effects. Speaking involves selecting a word among co-activated words in the lexicon. The factors determining which potentially co-activated words affect the production of spoken words remain underspecified. This research investigated the influence of words that sound similar to a target word (phonological neighbours) on the picture naming latency and accuracy of young English-speaking adults. Response time analyses showed a significant interaction between the frequency of the target and the frequency of those phonological neighbours that were higher in frequency than the target. Analysis of a published picture naming dataset gave similar results. The mechanisms underlying these results were explored using computational modelling. The critical interaction observed in the human data was successfully reproduced in analyses of the output of some versions of an interactive activation model. This model featured a relatively slow rise of activation in the phonological lexicon nodes, resulting in an increase in the effect of frequency. Overall, results show that phonological neighbourhood effects are tightly related to frequency effects.