A new species of the widespread genus Mesophyllum Lemoine is described. Mesophyllum macedonis nov. sp. grows in shallow (c. 0·5 m depth) waters, tolerating wide temperature fluctuations (12–26 °C) at a salinity of 32–35‰, protected from direct wave and light exposure. The species forms weakly attached rose-coloured clumps with whitish margins on rocky substrata. Its thallus is composed of superimposed foliose lamellae (to 170 μm thick) with dorsiventral organization, non-coaxial hypothallium, limited perithallial growth (to 60 μm thick), rectangular epithallial cells and solitary terminal trichocytes. Tetrasporangial conceptacles are raised and have convex roofs perforated by up to 108 pores that are bordered by filaments composed of slender and occasionally elongated cells. Tetrasporophytes were first observed in 1984 and their occurrence monitored without finding gametophytes or other populations at the type locality or elsewhere on the coast of the Sithonia Peninsula. A comparative study of literature data and material of selected congeners shows that M. macedonis shares most of its characters with M. ornatum (Foslie et Howe) nov. comb. from the Bahamas and Mariana Islands, and M. incisum (Foslie) Adey from southern Australia and New Zealand. Biogeographic scenarios that may explain the restricted distribution of the new Mediterranean endemic are discussed.