BACKGROUND: Transforming growth factor-ß (TGF-ß) is a major regulator of the synthesis of extracellular matrix (ECM) proteins in human skin as it stimulates fibroblast proliferation and collagen production. Perturbed TGF-ß expression may play a key role in the pathogenesis of skin aging. OBJECTIVES: This study was conducted to objectively evaluate the effects of different modalities of non-invasive facial rejuvenation on TGF-ß expression and to correlate its level with that of newly synthesized collagen. METHODS: A total of 36 patients with Fitzpatrick skin types III and IV were divided into six groups. Each group of six patients was subjected to a different non-invasive modality for the treatment of skin aging, including radiofrequency (RF), Nd:YAG 1320-nm laser and Er:YAG 2940-nm laser mini-peels, intense pulsed light (IPL), mesotherapy injection, and electro-optical synergy (ELOS). Skin biopsies were obtained before treatment, at the end of treatment, and at three months post-treatment. In addition, biopsies were obtained from 30 control subjects. Levels of TGF-ß were quantitatively evaluated using computerized image analysis of immunostained sections. RESULTS: The expression of TGF-ß was statistically significantly increased (P < 0.05) at the end of Nd:YAG 1320-nm and Er:YAG 2940-nm mini-peel treatments compared with baseline levels, and at three months post-treatment with RF and ELOS compared with pretreatment and end-of-treatment levels. However, no significant differences (P > 0.05) were observed in TGF-ß level in response to IPL or mesotherapy treatments in comparison with baseline. The level of TGF-ß was positively correlated (P < 0.05) to that of newly synthesized collagen at the end of Nd:YAG 1320-nm laser and Er:YAG 2940-nm laser mini-peels, as well as at three months after RF and ELOS treatments. CONCLUSIONS: Radiofrequency, ELOS, and Nd:YAG 1320-nm laser and Er:YAG 2940-nm laser mini-peels resulted in an increase in TGF-ß expression, which may mediate the effects of these modalities in enhancing dermal collagen expression through the activation of fibroblasts and thereby reverse the photoaging of skin.