We have previously reported possible evidence for linkage between manic depressive illness and the locus at 16p13.3 encoding the enzyme phosphoglycolate phosphatase (PGP), in the larger of two Danish families. As PGP was not fully informative, 12 additional DNA markers were tested in these families to clarify if a gene involved in the etiology of manic depressive illness might be located on chromosome 16p13. Though not reaching a lod score level of 3.0, the possible presence of a disease gene for manic depressive illness on chromosome 16p13 was still suggested. The evidence for a dominant locus near PGP was weakened. However, when assuming a recessive mode of inheritance and including both families a two-point lod score of 2.52 was found for marker D16S510, and a three-point lod score of 2.65 in both families combined and 2.29 in the large family alone was obtained in the same area. Simulations indicated that lod scores as obtained for several markers in the large family alone, would occur only rarely with an unlinked marker.