Purpose: Methamphetamine (MA) addiction is a significant problem in rural areas of the United States. Yet, little theoretically driven formative research has been conducted on the interactions of factors influencing initiation. The study was guided by Bronfenbrenner's bioecological model. Methods: Eighty-three MA users participated in an interview. Quantitative data included sociodemographic characteristics, drug use history, and psychosocial functioning. Semistructured interviews examined MA use histories with a focus on initiation. Transcripts of the interviews were coded for 5 themes related to Bronfenbrenner's influences including individual motivation, family, peers, work or school, or community as factors influencing initiation of MA use. Five dummy variables representing the presence or absence of a mention of Bronfenbrenner's 5 influences were created from the qualitative codes and entered into a hierarchical cluster analysis. Findings: The analyses revealed 4 distinct clusters: (1) predominantly female, influenced by peers and individual curiosity, (2) predominantly female, youngest age of first use, influenced by a family culture of drug use, (3) predominantly male, older age at first use, influenced by work settings and family co-workers, and (4) predominantly male, older age at first use, in the school context with a desire to increase intimacy. Conclusions: Bronfenbrenner's bioecological model was useful for classifying initiating influences and grouping individuals based on different combinations of influences. Identifying combinations of initiating factors such as work and community may facilitate tailoring of prevention programs, which may maximize efficacy and cost-effectiveness.