Cercariae of Diplostomum spathaceum penetrate the skin of fish, and then migrate along blood vessels and tissues towards the head and the eye-lens. We studied their orientation behaviour in tail fins of guppies and in chemical concentration gradients within agar-filled choice chambers. In fins, they entered veins and orientated cranially, independent of the blood flow and living cells. In choice chambers, they were attracted by a small molecular fraction of fish serum, D-glucose (at 1, 10, and 1000 μm), D-mannose, D-maltotriose and Cl-ions, whereas D-glucosamine repelled them (even at 1·0 nm). Amino acids were not attractive, but arginine in tetrapeptides attracted at concentrations as low as 1 μm and melatonin at 0·4–4·3 pm. We suggest a preliminary model for the behaviour of diplostomula in fish fins and attracting (+) or repelling (−) host cues: (1) migration towards deeper skin layers and avoidance of skin surface, cues: Cl-ions (+ and −), glucose (+), glucosamine (−), light radiation (−); (2) orientation in cranial direction, cue: Cl-ions (+); (3) localization of blood vessels, cues: glucose (+), arginine-residues (+); (4) localization of the retina, cue: melatonin (+). A comparison with the navigation mechanisms of tissue-migrating schistosomules and hookworm larvae reveals an enormous diversity of strategies.