Conformational analysis of highly substituted porphyrins has potential implications for modeling the behavior of macrocycles in tetrapyrrole-containing protein complexes and during catalytic reactions. In order to study the influence of different substituent patterns on the conformation of the porphyrin macrocycle, a series of metal free and nickel(II) decasubstituted porphyrins bearing aryl or ethyl groups at opposite meso positions and alkyl groups at the pyrrole positions have been synthesized and characterized by X-ray crystallography. Crystal structures of the flee-base porphyrins with 5,15-diaryl substituents showed negligible out-of-plane distortion but a large amount of in-plane distortion along the 5,15-axis accompanied by large bond angle changes similar to those previously seen for related porphyrins with 5,15-dialkyl substituents. Nickel(II) complexes of the 5,15-diaryl-substituted porphyrins show planar or modestly nonplanar conformations, suggesting that these complexes are not intrinsically nonplanar, whereas a complex with 5,15-diethyl substituents has a very ruffled conformation similar to those observed for related complexes with other metals. The nickel(II) complexes are also elongated along the 5,15-axis in a qualitatively similar but less dramatic fashion than are the free-base porphyrins. Spectrosopic studies (H-1 NMR, optical, and resonance Raman spectroscopy) suggest that conformations similar to those determined by X-ray crystallography are present in solution for the 5,15-dialkyl- and 5,15-diaryl-substituted porphyrins. Several asymmetric nickel(II) and metal-free deca- and undecasubstituted porphyrins containing both aryl and alkyl mesosubstituents were also investigated. Metal-free 5,15-disubstituted porphyrins with one aryl and one alkyl group showed considerably elongated porphyrin cores, whereas nickel(II) complexes of porphyrins with 5,10- or 5,10,15-substitution patterns showed very nonplanar structures consisting mainly of ruffle and saddle type distortions.