The aim of this study was to clarify the melanogenesis-inhibitory and antioxidant activity of Thai breadfruit's heartwood extract for application as a skin-lightening agent. The heartwood of breadfruit (Artocarpus incisus ) grown in Phitsanulok Province, Thailand, was extracted by using diethyl ether or methanol. The amount of artocarpin, a major component of A. incisus extract, was determined by using the HPLC method. The artocarpin content found in ether extract was 45.19 +/- 0.45% w/w, whereas that in methanol extract was 19.61 +/- 0.05% w/w. The ether extract was then evaluated for tyrosinase-inhibitory, melanogenesis-inhibitory, and antioxidant activities. The tyrosinase-inhibitory activity was tested in vitro by monitoring the inhibition of the extract against the formation of DOPAchrome by tyrosinase enzyme. The results showed that the tyrosinase-inhibitory activity of the extract was in a dose-dependent manner. The obtained IC50 value was 10.26 +/- 3.04 microg/ml, while kojic acid, a well-known tyrosinase inhibitor, provided an IC50 of 7.89 +/- 0.18 microg/ml. Melanocyte B16F1 melanoma cells (ATCC No. CRL-6323) were then used for determination of the melanogenesis-inhibitory activity of the extract, comparing it to hydroquinone, kojic acid, and purified artocarpin. The amount of melanin produced by the cells was monitored by measuring an absorbence at 490 nm. The obtained results indicated that A. incisus extract at a concentration of 2 to 25 microg/ml was able to decrease the melanin production of the melanocyte B16F1 cells. The obtained micrograph also confirmed that the extract did not change the cell morphology but reduced the melanin content by inhibiting melanin synthesis, whereas the purified artocarpin at a concentration of 4.5 microg/ml caused changes in cell morphology. Additionally, the extract exhibited antioxidant activity in a dose-dependent manner at an EC50 of 169.53 +/- 9.73 microg/ml, according to DPPH assay. The obtained results indicated that the ether extract of A. incisus 's heartwood has the potential of acting as a skin-lightening agent for application in cosmetics.