Medulloblastoma (MB) is a primitive neuroectodermal tumour of the cerebellum whose pathogenesis is poorly understood. Previous studies suggest a role for loci on chromosomes 11p and 17p in the pathogenesis of MB. Evidence for another potential MB locus has recently emerged from studies on Gorlin syndrome (GS), an autosomal dominant syndrome with multiple basal cell carcinomas, epithelial jaw cysts, and skeletal anomalies. Since GS can be associated with MB, we examined sporadic (non-GS) cases of MB for evidence of loss of heterozygosity (LOH) on chromosome 9 where a putative GS locus has been localized to band q31. Nineteen paired blood and MB DNA specimens from 16 patients (11 primary tumours, two primary with recurrent tumours, one primary tumour and cell line, two cell lines) were studied by PCR analysis of microsatellites at D9S55 (9p12), D9S15 (9q13-q21.1), D9S127 (9q21.1-21.3), D9S12 (9q22.3), D9S58 (9q22.3-q31), D9S109 (9q31), D9S53 (9q31), GSN (9q33), D9S60 (9q33-q34), D9S65 (9q33-q34), ASS (9q34), D9S67 (9q34.3), TH (11p15.5), D11S490 (11q23.3), D17S261 (17p11.2-12), D17S520 (17p12), TP53 (17p13.1), D17S5 (17p13.3), D17S515 (17q22-qter), and by RFLP analysis at the WT-1 locus (11p13). Only two tumours had LOH on 9q. One was non-informative at D9S15, D9S65, and GSN but showed LOH at D9S127, D9S12, D9S58, D9S109, D9S53, D9S60, ASS, and D9S67. The other was uninterpretable at D9S65 and non-informative at D9S15, D9S58, D9S53, and D9S67 but exhibited LOH at D9S127, D9S12, D9S109, GSN, D9S60, and ASS. Both these cases were informative at D9S55 without LOH.(ABSTRACT TRUNCATED AT 250 WORDS)