In the yeast Hansenula polymorpha peroxisomes are selectively degraded upon a shift of cells from methanol to glucose-containing media. We identified the H. polymorpha TUP1 gene by functional complementation of the peroxisome degradation deficient mutant pdd2-4. Tup1 proteins function in transcriptional repression of specific sets of genes involved in various cellular processes. Our combined data indicate that H. polymorpha TUP1 is involved in regulation of the switch between peroxisome biogenesis and selective degradation. The initial DNA fragment that complemented H. polymorpha pdd2-4 contained a second gene, encoding H. polymorpha Vps4p. Deletion of the VPS4 gene did not affect selective peroxisome degradation.