The activity of two tetracyclic psoralen derivatives and two furocoumarin isosters (pyrrolocoumarins) has been studied; by UVA light activation both tetracyclic psoralens are capable to photoreact with DNA and so inducing a strong inhibition of DNA synthesis in Ehrlich ascites cells, while the pyrrolocoumarins appeared to be no photobiologically active. On the other hand, all four compounds seemed to be very effective by simple incubation in the dark in the same test; in addition, in CHO cells a large number of chromosome aberrations (chromatid and chromosomal breaks, chromosomal rings and chromosomal interchanges) has been observed. On the contrary, in prokaryotic organisms, such as E.coli B48, they are poorly active. This dark activity cannot be at present explained, because the data until now obtained on their interaction with DNA in vitro have given inadequate results to conclude it is on the bases of their activity in the dark.