This multiple-probe study examined the effects of self-regulation on the acquisition of science vocabulary by four third-grade English language learners (ELLs) with learning difficulties. The students were provided only direct vocabulary instruction in a baseline phase, followed by intervention and maintenance phases into which self-regulation strategies were incorporated. Analysis of data derived from quantitative measures of receptive and expressive vocabulary revealed participants performed significantly higher in the intervention and maintenance phases than in the baseline phase, indicating the positive effect of self-regulation on science vocabulary learning. Furthermore, in interviews, although the participants were positive in their evaluation of the intervention overall, they expressed a distinct preference for the use of self-regulation strategies. Implications for practice and further research are discussed. (Contains 3 tables and 3 figures.)