This multiple-study experiment evaluated the utility of assessing and treating severe self-injurious behavior (SIB) based on the outcomes of a functional analysis of precursor behavior. In Study 1, a precursor to SIB was identified using descriptive assessment and conditional probability analyses. In Study 2, a functional analysis of precursor behavior was conducted. Finally, Study 3 evaluated the effects of a treatment in which precursor behavior produced the maintaining variable identified in the precursor functional analysis. Studies 1 and 3 were conducted in two settings in the participant's natural environment, where data collection was ongoing throughout the course of the study. Results showed that it was possible to identify a precursor to infrequent but severe SIB, that a functional analysis of precursor behavior suggested a clear operant function, and that treatment based on the results of the precursor functional analysis reduced SIB in the natural environment.