Clonal karyotype, clinical and blast cell features were established in 113 adults, aged 15-68 (mean 31.2) years with acute lymphoblastic leukemia (ALL). The karyotypes were: Philadelphia positive (Ph+), 23 cases; t(4;11), six cases; other chromosome findings (group II), 84 cases. Ph+ patients were older (mean 39.7 years) at presentation than the group II patients (mean 28.3 years) (p less than 0.0001). Ph+ was less frequent than expected in teenagers (15-20 years) (10.3%) and patients aged 21-50 years (21.8%), and more frequent in patients over 50 years old (43.8%) (p less than 0.01). Follow-up (between 0.5 and 4.5 years) was obtained for 108 patients. Age and karyotype (Ph+ versus group II) were prognostically significant for event-free (EFS) and overall survival (S) (p less than 0.001 in each instance). Ph+ patients fared worse than group II cases in all age groups, but karyotype added prognostic significance to age only when Ph+ and t(4;11) cases were combined (group I) (group I versus group II: EFS, p = 0.054; S, p = 0.043). The Ph breakpoint location M-bcr+ (nine cases) and M-bcr- (14 cases) was irrelevant to age (mean 37.7 and 41.3, respectively) and to prognosis. The findings indicate a fundamental difference between the genetics of ALL in most older and the majority of younger patients which may partly explain the increasingly poor prognosis with age.