OBJECTIVE To determine whether the federal regulation of ephedrine and pseudoephedrine, precursors used in illicit methamphetamine production, reduced methamphetamine-related acute care hospital admissions. METHODS ARIMA-intervention time-series analysis. METHODS California (1983-2000), Arizona and Nevada (1991-2000), USA. METHODS Monthly counts of methamphetamine-related acute care hospital admissions. METHODS Bulk powder ephedrine and pseudoephedrine: regulated November 1989. Products containing ephedrine as the single active medicinal ingredient: regulated August 1995. Products containing pseudoephedrine: regulated October 1997. Large-scale producers used ephedrine and pseudoephedrine in these forms. Ephedrine combined with other active medicinal ingredients (e.g. various cold medicines), used mainly by small-scale producers: regulated October 1996. RESULTS In California, the bulk powder regulation stopped a 7-year rise in admissions (1983-89) and reduced them by 35% (P < 0.01). The single ingredient ephedrine regulation stopped a 4-year rise (1992-95) in California, Arizona and Nevada, with 48% (P < 0.01), 71% (P < 0.01) and 52% (P < 0.01) reductions, respectively. The pseudoephedrine products regulation stopped a 2-year rise (1996-97) in California, Arizona and Nevada, with 38% (P < 0.01), 41% (P < 0.05) and 61% (P < 0.01) reductions, respectively. Admissions rose at the end of the study period but were still well below peak 1990s levels. The regulation of ephedrine combined with other active medicinal ingredients had no significant impact in any of the three states. CONCLUSIONS Regulations targeting precursors used by large-scale producers reduced admissions substantially during the study period. However, the regulation of precursors used primarily by small-scale producers had little, if any, effect.