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More than 95% of patients with SMA lack a functional <jats:italic>SMN1<\/jats:italic> but retain at least one copy of <jats:italic>SMN2<\/jats:italic>. Unlike <jats:italic>SMN1<\/jats:italic>, <jats:italic>SMN2<\/jats:italic> is primarily transcribed into truncated messenger RNA and produces low levels of SMN protein. We tested a therapeutic strategy by treating cultured lymphocytes from patients with SMA with hydroxyurea to modify <jats:italic>SMN2<\/jats:italic> gene expression and to increase the production of SMN protein. Twenty lymphoblastoid cell lines (15 SMA and 5 control lines) were treated with hydroxyurea at 5 concentrations (0.5, 5, 50, 500, and 5,000\u03bcg\/ml) and 3 time points (24, 48, and 72 hours). <jats:italic>SMN2<\/jats:italic> gene copy numbers were determined using real\u2010time quantitative polymerase chain reaction. Hydroxyurea treatment resulted in a time\u2010related and dose\u2010dependent increase in the ratio of full\u2010length to truncated SMN messenger RNA. SMN protein levels and intranuclear gems also were significantly increased in these hydroxyurea\u2010treated cells. The <jats:italic>SMN2<\/jats:italic> gene copy number correlated inversely with the SMA phenotypic severity. This study provides the first evidence for a therapeutic indication of hydroxyurea in SMA. 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