The telomeric P elements TP5 and TP6 are associated with the P cytotype, a maternally inherited condition that represses P-element-induced hybrid dysgenesis in the Drosophila germ line. To see if cytotype repression by TP5 and TP6 might be mediated by the polypeptides they could encode, hobo transgenes carrying these elements were tested for expression of mRNA in the female germ line and for repression of hybrid dysgenesis. The TP5 and TP6 transgenes expressed more germ-line mRNA than the native telomeric P elements, but they were decidedly inferior to the native elements in their ability to repress hybrid dysgenesis. These paradoxical results are inconsistent with the repressor polypeptide model of cytotype. An alternative model based on the destruction of P transposase mRNA by Piwi-interacting (pi) RNAs was supported by finding reduced P mRNA levels in flies that carried the native telomeric P elements, which are inserted in a known major piRNA locus.T RANSPOSABLE elements are significant components of the genomes of many organisms. These elements can cause gene mutations and chromosome breakage, and over evolutionary time, they can alter the composition and structure of genomes. There is, therefore, considerable interest in elucidating the mechanisms that foster or repress their activity. For example, many researchers have studied the regulation of P transposable elements in Drosophila melanogaster-a model family of elements in a model genetic organism (Engels 1989;Rio 1990).P elements are cut-and-paste transposons whose activity is catalyzed by an 87-kDa polypeptide, the P transposase, which is encoded by complete members of the P-element family (Karess and Rubin 1984;Rio et al. 1986). This polypeptide is restricted to the germ line because the last of the element's three introns is removed from P RNA only in that tissue . In somatic cells, retention of this intron results in the production of a 66-kDa polypeptide instead of the transposase. Tissue-specific splicing is therefore an important mechanism for controlling P-element activity. However even within the germ line, where the P transposase is made, P-element activity is regulated.Genetic evidence for this regulation was obtained from early studies that defined a maternally transmitted state called cytotype (Engels 1979;Kidwell 1981). The M cytotype permits P-element activity whereas the P cytotype represses it. Thus, when P elements are combined with the M cytotype by crossing P-bearing males to M-cytotype females, the P elements are mobilized in the offspring, where they cause a syndrome of germ-line abnormalities called hybrid dysgenesis (Kidwell et al. 1977;Engels 1989). This syndrome includes gonadal dysgenesis (GD) in both of the sexes, chromosome breakage, and elevated mutation rates. By contrast, crosses between P-bearing males and P-cytotype females produce offspring that seldom show dysgenic traits. These early studies also demonstrated that the P cytotype depends on the presence of P elements themselves (Engels 1979;Sved 1987); thus, t...