The thymidine kinase gene of herpes simplex virus I (tk) and pBR322 DNA (in a 1000-fold excess to tk) were introduced into mouse Ltk- cells by calcium phosphate DNA-mediated gene transfer. DNA fragments encompassing six junctions between the exogenous DNAs have been cloned and their nucleotide sequences determined. In all cases stretches of partial homology involving from 20 to 50 base pairs are present near the points at which joining occurs between the nonhomologous molecules. The results suggest that the recombination events involve the alignment of the two donor DNA molecules at partially homologous regions followed by asymmetric cutting and joining. One donor molecule is always cut in the region of homology while the second is cut at a small multiple of 13.5 (plus or minus) 0.5 base pairs away (0,14,27,39,41 and 54 base pairs). In the three junctions where the second cut is far from the region of homology, a 17 to 19 base pair segment of DNA separates the donor sequences. In all cases the origin of this "filler" DNA appears to be oligonucleotides derived from pBR322. In a related project we have subcloned eight junctions between exogenous DNA s and cellular DNAs. These insertion sites have also been sequenced. In order to determine whether the same rules of recombination apply to these events we are sequencing the cellular DNA before the integration event. We have also investigated the recombination of homologous overlapping fragments of tk (a selectable marker gene) transferred into Ltk- cells. The results show that recombination can occur at a high frequency and that small stretches of homology are sufficient. Two clinical case reports have analyzed patients with unusual genetic problems. In one a phenocopy of the fetal amniopterin syndrome was identified in a child where no maternal ingestion of folic acid antagonists could be documented. In another we examined three generations of a kindred with congenital contractural arachnodactily (CCA). Six of the seven patients examined had mitral valve prolapse. This association of cardiac involvement with CCA further lessens the distinction between CCA and the Marfan syndrome.